Batch filtration system for preparation of sterile fluid for renal replacement therapy

ABSTRACT

A method and device for blood treatments that use fluids such as dialysate and replacement fluid for renal replacement therapy. In an embodiment, fluid is passed either by pump or passively by gravity feed, through a microporous sterilization filter from a fluid source to a replacement fluid container. The latter forms a batch that may be used during treatment. The advantage of forming the batch before treatment is that the rate of filtering needn&#39;t match the rate of consumption during treatment. As a result, the sterilization filter can have a small capacity. In another embodiment, a filter is placed immediately prior to the point at which the sterile fluid is consumed by the treatment process. The latter may be used in combination with the former embodiment as a last-chance guarantee of sterility and/or that the fluid is free of air bubbles. It may also be used as the primary means of sterile-filtration.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. application Ser. No.12/786,255, filed May 24, 2010, now U.S. Pat. No. 7,976,711, which is acontinuation of U.S. application Ser. No. 12/434,246, filed May 1, 2009,now U.S. Pat. No. 7,749,393, which is a continuation of U.S. applicationSer. No. 11/160,764, filed Jul. 7, 2005, now U.S. Pat. No. 7,544,300,which is a continuation of International Application No. PCT/US04/00476,filed Jan. 7, 2004, which claims the benefit of U.S. ProvisionalApplication No. 60/438,567, filed Jan. 7, 2003, expired, all of whichare hereby incorporated by reference herein in their entireties.

BACKGROUND OF THE INVENTION

During hemofiltration, hemodialysis, hemodiafiltration, ultrafiltration,and other forms of renal replacement therapy, blood is drawn from apatient, passed through a filter, and returned to the patient. Dependingon the type of treatment, fluids and electrolytes are exchanged in thefilter between a dialysate and/or extracted from the blood byfiltration. One effect may be a net loss of fluid and electrolytes fromthe patient and/or exhaustion of dialysate, with a concomitant need forits replenishment, again depending on the type of treatment. To replacefluid lost from the patient and keep the patient from dehydrating,replacement fluid may be injected into the patient at a rate thatmatches a rate of loss, with an adjustment for a desired net change inthe patient's fluid complement. To replace exhausted dialysate, freshdialysate is continuously circulated through the filter.

Conventionally, dialysate and/or replacement fluid is supplied fromeither of two sources: batches of fluid, typically in multiple bags, ora continuous source of water that is sterile-filtered and added toconcentrated electrolytes to achieve the required dilution level.Because replacement fluid is injected directly into the patient,replacement fluid must be sterile. When either method is used togenerate replacement fluid, there is a risk of contamination of thefluid. Contamination may occur, for example, at the point where bags offluid are accessed (“spiked”) or at any connection in the fluid circuitlinking the source to the patient.

In many instances, such therapies may require a large quantity ofsterile fluid. A typical way to provide the large quantity ofreplacement fluid is to provide multiple bags of replacement fluid,dialysate, or infusate. The connection of these bags of fluid to anextracorporeal blood circuit, there is a risk of touch-contaminationresulting in the introduction of biological contaminants into thefluids. Presently, methods of producing large volumes of dialysate fromtap water are known, but each requires complex water purification andstandardization equipment, since impurities and cleaning additives suchas chlorine vary greatly in tap water from municipality to municipalityand within a municipality over time. (See Twardowski U.S. Pat. Nos.6,146,536 and 6,132,616.) Moreover, dialysate solution, whether preparedonline or prepackaged, while of the proper concentration for use as asterile replacement fluid, never enters the patient's body. Instead,dialysate flows past a semipermeable membrane that permits ions to beexchanged across the membrane until a balance between theirconcentrations in blood and their concentrations in the dialysis isachieved. This is effective to remove impurities from the blood and toadd missing electrolytes to the blood. Because it does not have to beinfused, dialysate is less expensive than solutions prepared asreplacement fluids, which are injected directly into a patient.

Attempts to render dialysate sufficiently sterile for use as areplacement fluid in hemofiltration and hemodiafiltration have focusedon continuous sterilization processes that require a separate dialysatefiltration/purification apparatus that must be periodically purged andverified to provide sufficient constant flow of sterile replacementfluid required for hemofiltration. (See Chavallet U.S. Pat. Nos.6,039,877 and 5,702,597.) Such devices are necessarily complicated andrequire separate pumping systems for the sterilization process. Inaddition, the rate of supply of dialysate for such systems is very high,requiring an expensive filter to be used. The same high-rate problemexists for the generation of replacement fluid for hemofiltration, andtherefore also requires an expensive filter.

SUMMARY OF THE INVENTION

In the present invention, sterile replacement fluid or dialysate may begenerated in batch form by sterile-filtering. According to embodimentsof inventions disclosed, non-sterile fluid is passed through a filterprior to treatment to prepare a batch of replacement fluid. This processmay be permitted to take any length of time because the rate of flow ofnon-sterile replacement fluid (or components thereof) through the filteris completely independent of the rate of consumption by the renaltherapy. Because the filters used for sterile-filtering tend to beexpensive, it may be desirable for such a batch process to employ asmall filter for such filtration. Such a filter can have a flow capacitythat is much lower than that required for real-time filtering of thereplacement fluid (or components). In addition to preparation of sterilefluid from non-sterile fluid, embodiments of inventions disclosed may beused to sterilize already-sterile fluid as a precaution against touchcontamination.

Generally replacement fluid is heated before being infused into apatient. This is often accomplished by heating the fluid as it is beinginfused with a heater with sufficient heating capacity. The capacity ofthe heater must be matched to the mass flow of the fluid and thetemperature rise required. In a batch preparation process, where a batchof fluid is prepared over a substantial period before use, a smallheater may heat the replacement fluid over a long period of time.Insulation may be provided to prevent heat loss. An insulating outercontainer for the sterile replacement fluid may be provided. Forexample, the container may be an insulated box with room for one or morelarge disposable sterile bags of the type normally used for infusiblefluids.

The preparation of warm sterile replacement fluid may be automated by acontrol process that permits a user to set up the fluids and othermaterials well in advance of a scheduled treatment. The process wouldensure that the replacement fluid is sterilized and heated to the propertemperature when the treatment is to begin.

The automation process may be permit the user to select how far inadvance of the treatment the preparation should be performed. This maybe useful, for example, where a particular source of replacement fluidhas proved to release more than a usual quantity of dissolved gases uponheating. Heating the replacement fluid and permitting it to settle for atime before it is used may allow gases to come out of solution andsettle at the top of the batch vessel or vessels. The automation processmay be incorporated in the control functions of renal therapy machine.

The invention or inventions will be described in connection with certainpreferred embodiments, with reference to the following illustrativefigures so that it may be more fully understood. With reference to thefigures, it is stressed that the particulars shown are by way of exampleand for purposes of illustrative discussion of the preferred embodimentsof the present invention or inventions only, and are presented in thecause of providing what is believed to be the most useful and readilyunderstood description of the principles and conceptual aspects of theinvention or inventions. In this regard, no attempt is made to showstructural details of the invention in more detail than is necessary fora fundamental understanding of the invention or inventions, thedescription taken with the drawings making apparent to those skilled inthe art how the several forms of the invention or inventions may beembodied in practice.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a standalone/retrofit apparatussystem for batch filtration of a sterile replacement fluid.

FIG. 2 is a flow chart illustrating an exemplary control procedureapplicable to various embodiments of the invention including those ofFIGS. 1 and 3.

FIG. 3 is a schematic illustration of a blood treatment machine with anattached subsystem for batch preparation of sterile replacement fluid.

FIGS. 4A and 4B are illustrations of fluid filters that may be use invarious embodiments of the invention.

FIG. 5 illustrates an exemplary blood treatment system with a filterused to sterilize and/or degas replacement fluid during treatment.

FIGS. 6-8 illustrate a blood treatment machine and cartridge providingvarious supporting mechanical features for the embodiment of FIG. 5 andfurther embodiments, including one in which a quality of replacementfluid is sensed before infusion.

FIG. 9 illustrates a disposable fluid circuit kit which may supportvarious embodiments of the invention.

FIG. 10 illustrates a set up for priming a blood treatment process,which components of the invention may be used to support.

FIG. 11 illustrates a portion of a blood treatment machine that allows apump used as part of the blood treatment to also be used to control thefiltering of fluid to provide a batch of infusible replacement fluid.

FIG. 12 illustrates replacement fluid container tubing set.

FIG. 13 illustrates a replacement fluid preparation apparatus.

FIGS. 14, 15, and 16 illustrate portions of the replacement fluidpreparation apparatus of FIG. 13.

DETAILED DESCRIPTION

Referring to FIG. 1, a filter 160 filters fluid from a source of fluid150 to generate a batch of sterile replacement fluid 130. The filter 160may be, and preferably is, a microporous filter that blocks allmaterials except dissolved electrolytes and water. Thus, the result ofthe filtration process is to sterilize the raw fluid from the source offluid 150. The source of fluid 150 may be a container of sterile ornon-sterile replacement fluid, one or more containers of constituentswhich, when combined, form a proper replacement fluid. Any of the lattermay include a continuous source such as a water tap. One or more conduitelements form a line 120 to convey the source fluid 150 through thefilter 160 and into a batch container 147.

The latter may be any type of sterile, preferably disposable container,for example, a large IV bag. It may also include a number of suchcontainers appropriately interconnected to permit flow into and out ofthem in the fashion of container 147.

Included in the conveyance from source fluid 150 to sterile replacementfluid 130 may be a pump 190, such as a peristaltic pump. The pressure atan outlet of the filter 160 may be sensed by a pressure sensor 162 andthe pump 190 controlled by a controller 170 to insure a predefinedtransmembrane pressure (TMP) threshold of the filter 160 is notbreached. The TMP may be maintained at a maximum safe level to maximizethroughput. Note that complexity may be avoided if the source fluid 150is arranged such as to maintain a desired TMP at the filter 160 withoutthe need of a pump 190 or pressure sensor 162. For example, the sourcefluid 150 may be provided by a batch container elevated at a certainheight to provide a desired head. Note that a control valve 165 or aspeed of the pump 190 may be used to regulate the flow rate to maintaindesired TMP limits.

A control/shutoff valve 180 may provide the controller 170 the abilityto stop the flow of fluid through the filter 160 once a desired volumeis reached. A heater 185 may be provided to warm the sterile replacementfluid 130 to prepare it for use. An insulated container 145 may be usedto reduce heat loss so that heater 185 can be a relatively low powertype. The heater 185 may be controlled by the controller 170 to ensurethe replacement fluid 130 is at a desired temperature when required tobe used. Alternatively the heater 185 can be controlled by anindependent device actuated by, for example, a pressure sensor (notshown) triggered by the flow of fluid into the batch container 147, atimer (not shown) settable to trigger based on a predefined treatmenttime, or some other means. Preferably, in either case, a temperatureregulator (e.g., a temperature sensor 183 combined with logic incontroller 170) regulates power to the heater to ensure a requiredtemperature is maintained and not exceeded. The temperature sensor 183may be used to sense the quantity of sterile replacement fluid by therate of detected temperature increase versus heater output. Thetemperature sensor 183, heater 185, and sterile replacement fluid 130can be modeled in any desired fashion. For example one may neglect allbut the thermal mass of the RF, assume perfect heat transfer (includingassuming the RF fluid to be isothermal). Then, the mass would be givenby the product of the temperature change, the thermal capacitance of thefluid, and the heat output rate of the heater. More complex theoreticalor empirical algorithms would be a simple matter to derive andimplement. Once the mass of fluid is calculated to be below a certainlevel, the controller 170 may be programmed to respond in accord withthe assumption the sterile RF is exhausted. Equivalently, the controller170 may simply respond to some predefined rate of temperature rise ofthe temperature sensor 183.

When the temperature of the sterile replacement fluid 130 is raised,dissolved gas may come out of solution. This may cause bubbles toaccumulate inside the replacement fluid container 247, which isundesirable because of the risk of infusing bubbles into the patient'sbloodstream. To help ameliorate that problem, a vibrator or ultrasonictransducer may be provided 183 to cause bubbles to coalesce and rise toa top of the container 147. As a result, bubble-free replacement fluidmay be drawn through the outlet 148.

A connector 195 may be provided for connecting the source fluid to theline 120. The connector may be a luer, spike, threaded adapter, or anyother suitable type. Although the various controls indicated above areshown to be controlled an automatic controller 170, each may becontrolled also by manual mechanisms.

The FIG. 1 embodiment allows replacement fluid to be prepared in batchfor later use. Thus, the rate of filtration of replacement fluid neednot match the requirements of the treatment process or preparatory stepssuch as priming. As a result, a low capacity filter may be used for thefilter 160. For example, typically only a small quantity of expensivemedia is required to make a small-capacity filter and as such, the costof a low capacity filter can be much smaller than a high capacityfilter.

Also, other features found in high capacity filters, such as a largeratio of media surface to volume of the filter module are achievableonly by means of folding or forming media into shapes that can bedifficult to manufacture, such as tubes. Thus, savings can be achievedin simplification of the configuration of the filter as well. Relativelysmall filters with simple planar media held in plastic casings areavailable and suitable for this purpose.

The configuration of FIG. 1 may be retrofitted for use with an existingtreatment system. For this purpose, the outlet 148 may provide with anyrequired connection adapter. A user interface 175 for entering data intothe controller 170 may be provided as well.

Referring now to FIG. 2, a control algorithm for controlling the heater185, pump 190, valves 165/180, etc. begins with the a setting of a timefor treatment 510, for example by entering a time into the controller170 via a user interface (UI) 175. The time can be entered manually orautomatically by means of, for example, a data signal from a remotesource via a switched or network circuit. The time for treatment may beobtained from a treatment calendar entered into the controller 170,which also may be obtained from a remote source. In the present simplealgorithm, first and second time intervals T1 and T2 are definedrepresenting the interval required for filtration of RF and the intervalrequired for heating of RF, respectively.

These values may be obtained from any of the above means (e.g., localmanual or remote entry via UI/interface 175) or from data encoded on oneof the consumables involved in the process. For example, the filter 160,the RF fluid container 147, the source fluid 150 container (s), or anyother consumable may be provided with one or more bar-codes, RFID tags,or other suitable encoding device. Such devices may provide values forT1 and T2, tables of values that depend upon other factors, or otherdata from which T1 and T2 may be derived.

The controller 170 waits until it is time to start the flow of raw RFfluid from source fluid 150 toward container 147 by comparing a currenttime (indicated by a clock internal to the controller 170, which is notshown) to a difference between a scheduled treatment time and T1, whichrepresents the lead time (ahead of the scheduled treatment) required forthe filtering process. A loop through step S20 is exited to step S30when the clock reaches the treatment time minus T1. At step S30, theflow of source fluid 150 through the filter 160 is initiated. If thepump 190 is present, it may be started and regulated according to aspecified TMP. The latter may be provided to the controller 170 manuallyor automatically through UI/interface 175. Automatic entry may be by wayof a data store such as bar-code or RFID attached to the filter, forexample which may be read when the filter 160 is installed in a chassiswith a corresponding reader device (not shown). Note, as mentionedabove, the source fluid may be sterile and the filtration processprovided as a guarantee against contamination, for example by accidentaltouching.

Once the flow of source fluid 150 is initiated, the controller waits forthe required time for applying power to the heater 185. The delay andthe initiation are controlled by step S40 which is exited to step S50only when the treatment time minus the predefined interval T2 isreached. As mentioned above, alternatively, the heater may be triggeredby detecting fluid such as by means of a sensor (not shown) triggered bythe presence of sterile replacement fluid 130 in the container 147. Thesensor may be any of a variety of types, such as an ultrasonic sensor,capacitance sensor, mass sensor, optical sensor, etc.

Once the heater is started, the controller 170 may wait for the sourcefluid to be exhausted at step S60. Step S60 exits to step S70 when thesource fluid is determined to be exhausted. The latter may be detectedby integrating the flow rate to measure the total volume (the rate maybe determined by the pumping rate, for example, or by a flow meter (notshown)). The exhaustion of the source fluid 150 may also be indicated bya quantity indicator (e.g., a level indicator) in the sterilereplacement fluid container 147 or an intermediate container suppliedthrough a drip chamber, for example. Alternatively, the exhaustion ofthe source fluid 150, if supplied from a fixed-volume container, may beindicated by a sensor such as an ultrasonic sensor, capacitance sensor,mass sensor, optical sensor, a scale, etc. Yet another alternative is tosense gas or a precipitous rise in negative pressure (sensed by apressure sensor which is not shown) at the pump 190 inlet. At step S70,the line 120 may be clamped by actuating shutoff/control valve 180.Additionally, if appropriate, the pump 190 may be deactivated at thepoint where the exhaustion of the source fluid 150 is detected at stepS70.

According to an embodiment, as the fluid is pumped, the TMP of thefilter, as indicated by pressure sensors 162, may be monitored. If theTMP is determined by the controller 170 to be, at any point, below apredetermined nominal value or to have changed precipitously duringfiltration, the controller 170 may trigger an alarm or take some otheraction to insure that the resulting replacement fluid is handledappropriately. For example, a back-up filter could be added duringtreatment as discussed with respect to FIG. 5. The TMP results couldtrigger an alarm at any point during filtration or could be assessed andreported at step S70, before treatment would begin.

The controller 170 pauses again at step S80 to wait for the sterilefluid to be exhausted. This may be indicated by a signal from thetreatment machine (e.g., received via UI/interface 175) or by directmeasurement by a sensor, such as an ultrasonic sensor, capacitancesensor, mass sensor, optical sensor, a scale, etc. As mentioned above,the controller 170, or the heater 185 itself, may be provided with athreshold temperature-rise rate that indicates the mass of fluid in thereplacement fluid container 147 has fallen below a minimum level. Theloop of step S80 is exited to step S90 where power to the heater 185 isterminated.

Note that all the functionality attributed to the controller 170 may beprovided, via a control interface, by a controller (not shown) internalto a treatment machine. For example, the apparatus of FIG. 1 could beprovided as an optional module for such a treatment machine rather thana retrofit module.

Referring now to FIG. 3, a combination blood treatment system andsterile replacement fluid device 310 has a replacement fluid preparationsubsystem 305 configured substantially as the device of FIG. 1. A filter260 filters fluid from a source of fluid 250 to generate a batch ofsterile replacement fluid 230 as in the embodiment of FIG. 1. Again, thesource of fluid 150 may be a container of sterile or non-sterilereplacement fluid, one or more containers of constituents which, whencombined, form a proper replacement fluid and any of the latter mayinclude a continuous source such as a water tap. A line 220 conveys thesource fluid 250 through the filter 260 and into a batch container 247,which may be any type of sterile, preferably disposable container, forexample, a large IV bag. It may also include a number of such containersappropriately interconnected to permit flow into and out of them in thefashion of container 247.

Again, a pump 290 may be provided and pressure at an outlet of thefilter 260 may be sensed by a pressure sensor 262. The pump 290 may becontrolled by a controller 270 to insure a maximum safe TMP to maximizethroughput. Again, the pump 290 is not required and the source fluid 150may be arranged such as to maintain a desired TMP at the filter 160without the need of the pump 290 or pressure sensor 262 by elevation. Acontrol valve 265 or a speed of the pump 290 may be used to regulate theflow rate to maintain desired TMP limits.

A control/shutoff valve 280 may provide the controller 270 the abilityto stop the flow of fluid through the filter 260 once a desired volumeis reached. A heater 285 may be provided to warm the sterile replacementfluid 130 to prepare it for use. An insulated container 245 may be usedand the heater controlled as discussed with respect to the FIG. 1embodiment. Bubbles may be controlled, as discussed above, by means of avibration or ultrasonic transducer 230 as discussed above with regard tothe previous embodiment.

A connector 295 may be provided for connecting the source fluid to theline 220. The connector may be a luer, spike, threaded adapter, or anyother suitable type. Although the various controls indicated above areshown to be controlled an automatic controller 270, each may becontrolled also by manual mechanisms. Other aspects of the controlmechanisms for the embodiment of FIG. 3 may be provided as discussedwith respect to FIGS. 1 and 2.

The benefits of the FIG. 2 embodiment are similar to those of the FIG. 1embodiment in that it allows replacement fluid over a time period thatis not driven by the speed of supply to the treatment process. As aresult, a low capacity filter may be used for the filter 260 with theattendant benefits identified above. Note that the UI/interface 275 andcontroller 270 are shared in the present embodiment by the treatmentmachine. Thus, any information required for control of both thetreatment and preparation of sterile replacement fluid 230 would notneed to be communicated to a separate controller such as controller 170.Note also that the communications among the illustrated components isprovided by a channel 202 which may be wire harness, separate wires, abus, a wireless channel or any suitable communications/powertransmission device.

In the embodiment of FIG. 3, a predicted quantity of replacement fluidmay be filtered and stored for use during treatment. If, however, forsome reason, more is required, the treatment machine controller 270could be configured to identify that situation and control the subsystem305 components to provide it. Many blood treatment process employ afilter 220 to filter blood and into which replacement fluid is suppliedto a patient 225. More details on preferred embodiments of the treatmentmachine are discussed below.

In either of the above embodiments, the rate of flow of fluid duringpreparation of the batch of replacement fluid may be substantially lessthan the rate of consumption during treatment. In an exemplaryembodiment of an application for hemofiltration, the amount ofreplacement fluid consumed is between 9 and 181, and the rate ofconsumption is approximately 200 ml./min. Also, the media used forsterile filtration may be any suitable media that insures the quality ofthe replacement fluid is as desired. In the embodiments discussed above,it was assumed that the end sought was preparation of sterilereplacement fluid employed microfiltration to prevent the passage ofpathogens. However, the invention could be used with other types offiltration or treatment processes to produce a batch of fluid consumedby a medical treatment process, for example, dialysate for hemodialysistreatment. The benefits accrue in particular when the time scale ofpreparation may be longer than the time scale of consumption. Moreover,the benefits are more appreciable when some sort of energy-consumingprocess is required, such as heating, before consumption.

Here, not only is the time scale of preparation compatible with a smallinexpensive filter, but the long time scale permits heating of thereplacement fluid over a long interval. To support this benefit, thebatch container may be insulated to minimize heat loss so a small heaterwill be adequate. Also, the preferred application for the presentinvention is in the context of hemofiltration because the quantity offluid required for such treatment is relatively small.

Note that other motivations for filtering the fluid, in addition to oras an alternative to sterilization of a non-sterile fluid, is (1)removal of air bubbles and/or (2) as a safety net for ensuring againstaccidental contamination. If bubble removal is the only concern, a dripchamber may be used instead of a filter. For removing bubbles, thefilter preferably is of a type that permits the passage of fluid, butwhich blocks the passage of bubbles, for example due to its media poresize and the surface tension of the fluid.

Referring now to FIG. 4A, a preferred type of filter for some of thepresent embodiments has an inlet port 415 providing an inlet channel 410communicating with an inlet chamber 440. An outlet leading port 405provides an outlet channel 420 communicating with an outlet chamber 445.A piece of filter media 425 separates the inlet and outlet chambers 440and 445. The fluid to be sterilized enters the inlet chamber 440, issterilized by passing through the filter media 425, and exits via theoutlet chamber 445. A gas relief gasket 425 allows gas accumulating inthe inlet chamber 440 to be released to the ambient atmosphere.

Internal supports and structural details are not shown in theillustration for clarity, but a practical embodiment of the filter ofFIG. 4 may have ribs for strength and internal supports for the media425 and gasket 425 so that the filter 400 may be capable of tolerating asubstantial TMP.

The gas relief gasket 425 may be of a porous hydrophobic material suchas PTFE. Air bubbles trapped in the inlet chamber 440 can coalesce inthe inlet chamber 440 and exit via the air relief gasket 425. It may be,depending on the type of gas relief gasket 425 used, that a substantialTMP will be required to eliminate air.

An alternative to the gas relief gasket 425 is a gas relief valve 426 asshown in FIG. 4B. Since the inlet chamber 440 is connected to thenon-sterile side of the filtration system, there is little risk ofcontamination if microbes were to enter through a mechanical device suchas the gas relief valve 426. The latter is illustrated figuratively andallows only gas to escape. Other features of the embodiment of FIG.

4B are labeled with the same numerals as features of the embodiment ofFIG. 4A where they serve substantially identical functions and, thus,their descriptions are not repeated here.

Referring now to FIG. 5, the filters of FIGS. 4A and 4B may be used forfiltration of replacement fluid in the embodiment of FIG. 5 as discussedpresently.

Replacement fluid 360, which may or may not be sterile, is supplied to ahemofiltration machine 490. A replacement fluid pump 360 pumps thereplacement fluid into a balancing mechanism 330 which meters thereplacement fluid before it is introduced, via a junction 485, into thevenous (return) line 480 and ultimately into the blood stream of apatient 225. Waste fluid is drawn through a waste line 470 from a filter395 and pumped via a waste pump 365 through the fluid balancingmechanism 330. The fluid balancing mechanism 330 meters the replacementfluid to match the rate of withdrawal of waste fluid so that thepatient's fluid balance is maintained during treatment. Actually, therate of withdrawal of waste fluid may be less than the rate of meteringof replacement fluid by pumping waste fluid through a bypass pump calledan ultrafiltration pump 339. The latter sends some of the waste fluiddirectly to a waste fluid sump 380, thereby bypassing the fluidbalancing mechanism 330. The fluid balancing mechanism is depictedfiguratively and may operate in accord with any suitable control device.Preferably it meters replacement fluid on an equal-volume or equal-massbasis. A preferred mechanism is described in U.S. patent applicationSer. No. 09/513,911, filed Feb. 25, 2000, entitled: “SynchronizedVolumetric Fluid Balancing Systems and Methods,” which is herebyincorporated by reference as if fully set forth in its entirety herein.Various sensors and line clamps, indicated figuratively at 335,355,320,385, and 390, may be provided to control flow and ensure safeoperation.

A filter 337, is provided in the replacement fluid line 338 justupstream of the junction 485. The filter 337 may serve as a last chancesafety net for ensuring that replacement fluid is sterile and/or thatall bubbles are removed before flowing into the venous line 480. Toensure that air is not infused into the patient's body, an air sensor390 is often provided in hemofiltration systems, but detection of airnormally triggers an alarm, automatic shutdown, and skilled interventionto restart the hemofiltration treatment. Obviously, this is undesirableso the system should, as effectively as possible, insure that air orother gas is not injected into the venous line 480.

Although in the embodiment of FIG. 5, a hemofiltration machine wasdiscussed, other types of treatment processes may be provided alast-chance filter similar to filter 337. For example,hemodiafiltration, hemodialysis, or other treatments may require theinfusion of replacement fluid and thereby benefit from a filter such asfilter 337. Preferably, the filter 337 is substantially as in theembodiment of FIG. 4A. Thus, the filter 337 removes both air andpathogens.

Instead of employing a filter at the location indicated at 337, a dripchamber may be used. Suitable drip chambers are currently available withair vents and microfilters effective to remove pathogens, so they may besubstituted for the filter 337. Also, in some cases, it may be thatthere is very little risk that the replacement fluid is contaminatedwith pathogens, the filter 337 may serve as a mechanism for removingonly air or other gases. In such cases, drip chambers which remove gas(either with or without a vent), could be employed at the above locationin the fluid circuit.

Referring now to FIGS. 6, 7, and 8 the last chance filter or dripchamber (or combination device) 510 may be installed in a cartridge 520that holds and orients blood and fluid circuits for a hemofiltrationmachine 540. In the embodiment shown, which is described substantiallyin U.S. patent application Ser. No. 09/513,773 filed Feb. 25, 2000 andentitled: “Fluid Processing Systems and Methods Using ExtracorporealFluid Flow Panels Oriented Within A Cartridge,” hereby incorporated byreference in its entirety as if fully set forth herein, fluid circuitcomponents may be held in a cartridge 520 and clamped (as shown in FIG.8 with the machine closing as illustrated by the arrow 665) within areceiving gap 530 in a blood treatment machine such as hemofiltrationmachine 540. The cartridge 520 may have a preferred orientation whichmay insure a correct orientation for the last chance filter or dripchamber (or combination device) 510 if required by the particular devicechosen. To insure orientation of the last chance filter or drip chamber(or combination device) 510, the latter is preferably held by thecartridge 520 in a fixed orientation with respect to the cartridge 520.

In an alternative embodiment, the last chance filter or drip chamber (orcombination device) 520 may be accompanied by a device 660 for measuringthe quality of the replacement fluid, such as conductivity or density.This may provide a last-chance check that the replacement fluid is ofthe correct type. For example, where such fluids are derived frommixtures, if the proportion is not exactly what is required, infusioncould be harmful to the patient 225. An example of a device 660 to testthe fluid could be a wettable pair of contacts (not shown) formed in atubing set 650 of the cartridge may be used in conjunction with aresistance measurement device to measure the ion concentration of thefluid. Alternatively, a non-wettable sensor, such as an ultrasonicconductivity cell could be used. Other kinds of fluid quality sensorscould be employed such as new types of specific-molecule detectors builton silicon wafers.

Preferably, the tubing set 650 and cartridge 620 of which it is a partform a disposable component that is used for one treatment and disposedof. Note that the fluid quality sensor 660 may used alone or togetherwith the last chance filter or drip chamber (or combination device) 510.Note, although FIGS. 6 and 7 are detailed, they are intended to showvarious components figuratively and do not reveal the details of therouting necessary to achieve the flow paths discussed with respect tothem or as illustrated elsewhere.

Referring now also to FIG. 9, the tubing set and cartridge assembly 610,discussed previously, may incorporate the batch replacement fluidcontainer 625 as part of a sterile replaceable set 690. The filter 615may have a tube 622 with a connector 620 for attachment to a sourcefluid 250. A tube 635 may connect the filter to the batch replacementfluid container 625, which may be fitted with another tube 630 to conveyfluid to the tubing set and cartridge assembly 610. Referring now alsoto FIG. 10, the batch replacement fluid container 625 may also be fittedwith additional connectors 670 and/or extensions (not shown) to permitthe batch replacement fluid container to be used for priming blood,replacement fluid, and/or waste lines. For example, as discussed in U.S.patent application Ser. No. 09/905,246, filed Jul. 12, 2001, entitled:“Devices and Methods For Sterile Filtering of Dialysate,” which ishereby incorporated by reference as if fully set forth in its entiretyherein, replacement fluid is circulated through a replacement fluidcontainer 740 to flush air out of all the fluid circuiting (not allshown) of a blood treatment apparatus 710. As described in detail in the'246 application incorporated by reference above, the venous (return)and arterial (supply) blood lines 725 and 730 may be temporarilyconnected via connectors 750 to the replacement fluid container 740 andfluid circulated through the container 740 until gas bubbles aresubstantially purged from the relevant circuits.

Note, the replacement fluid container 740 corresponds to the containers147 (FIG. 1), 247 (FIG. 3), and 625 (FIG. 9) in the foregoing figuresand to respective containers in the application incorporated byreference immediately above. The air and other gases may settle in thereplacement fluid container 740 as the fluid circulates. Liberation ofthe gases would ordinarily be promoted by the application of heat from aheater 775 (with power source 770), which may be employed as discussedwith regard to the embodiments of FIGS. 1-3 or in any suitable way tobring the temperature of the replacement fluid to body temperature.Replacement fluid circuits including line 735, blood circuits includinglines 725 and 730, and waste fluid circuits including line 780 may allbe flushed with fluid from the container 740. The details of the bloodtreatment apparatus and its internal plumbing can vary. Replacementfluid may be transferred from the replacement fluid line 735 or from theblood line 735 to the waste line, for example through a filter, to flushthe waste portion of the circuit including the waste line 780.Replacement fluid may circulate through the blood circuit includinglines 725 and 730 as indicated to flush the blood circuit, at least aportion of which may be closed as indicated by the arterial and venouslines 730 and 735.

Disposable components, such as the circuit sets of FIGS. 8 and 9 or thebatch replacement fluid container 625 alone, or other components thatmay be used with the embodiments disclosed may be packaged withinstructions for preparing infusible replacement fluid. For example, thesource fluid 150/1250 or a concentrate which may be mixed to make thesame (FIGS. 1 and 3) may be supplied with instructions for sterilefiltering the fluid as described in the instant specification. Such mayconstitute packages of consumables or reusable components.

Note that benefits of the filtering method and apparatus discussed abovemay best be achieved by performing the filtration just prior totreatment, although this is not required. The filtering method may beperformed at the treatment site. For example, non-sterile concentratemay be stored at the residence of a patient.

The concentrate may be diluted with distilled water in a source fluidcontainer (e.g., 196 of FIG. 1) at the residence and processed asdiscussed in the instant application.

Because the infusible fluid is generated at the treatment site, the needfor regulatory-cleared fluids, such as might be obtained from amanufacturer, is not avoided. Cost savings and storage-space economiescan thus be realized by the patient. This is particularly important inview of the fact that renal replacement therapies are often administeredmany times per week and storage and cost of consumables can present aserious problem in a residence or any other facility.

Referring now to FIG. 11, a blood treatment machine, a portion of whichis illustrated figuratively at 810, may permit a pump 845 that, duringtreatment, conveys replacement fluid to a patient, to be used forfiltering a sterile filtering a non-sterile source fluid. Here, themachine 810 has a common guide 850 that accommodates a fluid line 815through which fluid is conveyed by the pump 845, for example aperistaltic pump. During treatment, the line 815-825 may be guided by afirst selected guide 830 in a first direction toward other components ofan internal fluid circuit (not shown) as indicated at 825. Duringsterile-filtering, fluid may be pumped by the same pump 845 through aline 815-820 that is allowed to pass out of the blood treatment machine810 via a different guide 835. This allows the line 815-820 to be fed toan external connection to the sterile fluid container (not shown) asindicated at 820.

Referring now to FIG. 12, another embodiment of a replacement fluidcontainer portion of a disposable tubing set includes a replacementfluid container 1, a break-off female luer lock connector 4, ay-connector, 5, a pinch clamp 6, a male luer 8, a female luer 26, a 0.22micron pore anti pyrogen filter 11, a non reopenable tubing clamp 13, anon-breathing cap 14 on a femal luer 9, an in-line check valve 16, apinch clamp 18, a break-off male luer cap and female luer 19, and afemale luer 21 and tubing branches 3,7, 10,12, 15,17, and 20. Thereplacement fluid container 1 is delivered to a patient treatmentsetting as a sealed sterile container with all terminals sealed. Thereplacement fluid container contains, as delivered, a concentratesolution sufficient to create a treatment batch of replacement fluidwhen water is added.

Concentrate may be added by means of the luer connector 21. In thedeliverable to the treatment site, the tubing branch 20 may be sealedand cut after the concentrate is added. Water is added at the treatmentsite through connection to a water source via luer 19. The water ispreferably metered to provide a predefined quantity. The 0.22 micronfilter is sufficient to protect against contamination before water isadded to the replacement fluid container 1. A sample of dilutedreplacement fluid may be drawn through the luer 19 before treatment. Thecheck valve 16 prevents any contamination due to backflow from thesampling procedure. After water is added to the replacement fluidcontainer 1, the luer 9 is disconnected from the male luer 8 and themale luer connector connected to the blood treatment system.

To supply suitable water that is substantially free of unwanteddissolved and undissolved materials, a combination of permanent andreplaceable components may be provided at the treatment site. FIG. 13illustrates such a set up in overview fashion. A pretreatment module 900provides primary filtration from a raw water supply, for example tapwater and feeds prefiltered water to a controller module 905 whichprovides various control functions, a pump, pressure detection andcontrol, and permanent filtering capabilities which are not shownseparately here. Water is metered by the control module into aconsumable disposable module 910 which may provide deionization,adsorption filtration, microporous filtering, chemical pretreatment,etc. and any other types of filtering that may require replacement ofcomponents. The purified water is finally conveyed to the replacementfluid container circuit 915 discussed with reference to FIG. 12.

Referring to FIG. 14, pretreatment module 900 is shown in more detail. Acheck valve 955 prevents backflow. An air vent 953 removes air from theprimary supply and a sediment filter 951 (which may be replaceable)provides substantial filtering of solids.

Referring to FIG. 15, the control module 905 is shown in greater detail.A shutoff valve 1010 is provided for safety. Pressure indicators 1015and 1025 may be provided for monitoring the respective pressures in andout of a pump 1020.

Feedback regulation may be provided to ensure that consistent meteringis provided if the pump is relied upon for measuring the total quantityof water supplied to the replacement fluid container 1. A high intensityultraviolet (UV) lamp 1030 provides a sterilization mechanism.Preferably, the UV lamp 1030 is ov such intensity and wavelength as toprovide disintegration of chloramines. In a preferred embodiment, thelamp is characterized by a 245 nm wavelength and an output power of 750mJ/cm2 up to 1500 mJ/cm2 which is sufficient to remove chloramines.

Referring to FIG. 16, the replaceable (disposable or remanufacturable)filter module 910 contains a first stage filter 1007 copper-zinc alloywhich is used to subject the water to a reduction/oxidation process toremove ions. This removes ions through a chemical reaction. Anembodiment is KDF 85 media where about on pound is used for a flow rateof 150 ml./min water flow rate. A activated carbon filter 1005 followswhich is a well-known adsorption type filter. Next three stages ofstrong acid cation 1011 and strong base anion 1009 filters follow inseries. A sensor

1022 detects ion concentration by contact testing of the conductivity ofthe water. A signal is generated to indicate that this is the lastallowed batch before replacement of the replaceable module 910. A mixedbed deionoization filter 1030 is provided next and a safeguardconductivity test is provided with an audible alarm at 1025 as a back upsafety measure. If the conductivity it detects is above a certain level,the pump 1020 may be shut off and an alarm sounded. This may come intoplay if an operator ignores the tester 1022 which may provide a visualsignal or if the tester 1022 fails.

TP is a hydrophobic membrane air vent which allows air in an ultrafilter1035 to be purged. The ultrafitler 1035 may be a microtubular filtersuch as used for dialysis. A 1.2 micron air vent may also be provided asshown at 1047.

Note the final conductivity sensor/alarm 1025 may control the pump, asnoted. A controller 1090 may be connectable to the disposable filtermodule 910 and configured to stop the pump 1020. The trigger resistivitysafety level to cut-off the pump 1020 may be 1 megaohm, but may beraised to 2 megohm to allow the use of required temperature compensatedresistivity probes (an FDA & AAMI requirement) This does allow use oflow cost in-line resistivity probes in the disposable filter module 910.

The following is a procedure for using the above devices discussed withreference to FIGS. 12-16.

1. Remove the dialysate concentrate tubing set 915 and remove the cap 14from the tubing line 7 that contains the filter 11. (The 0.22 micronfilter 11 provides additional protection from inadvertentcontamination.)

2. Connect the water source to the concentrate bag luer connection 9.

3. Break the frangible luer connector 4 which connector is configured

to form a permanent seal on the side facing the Y-junction 5 whendisconnected.

4. Add 3 liters of water into the concentrate bag using the purificationplant through tubing branch 7 through luer connector 9.

5. Write on the bag label the date and time water was first added to theconcentrate bag, to assist in ensuring that it is used within 24 hours.

6. Shake the replacement fluid container 1 well to mix.

7. Confirm solution conductivity prior to use. Remove the break-off cap1 and draw sample from this branch 16. After removing the sample, clampthe line using the pinch clamp 18 provided.

8. (The following is normative according to a preferred embodiment andnot limiting of the invention) Conductivity must be in the range 13.0 to14.4 mS.

Nominal conductivity for the dialysate solution is 13.7 mS at 25 C. Ifconductivity does not meet this specification do not use it. Verify thatthe results are accurate. If conductivity is high additional water maybe added to bring it within specification. If conductivity is low thenthe solution must be discarded.

9. Using the non re-opening clamp 13 provided, clamp the line that isconnected to the water purification plant.

10. Using the clamp 6 is next clamped on the line that is connected tothe dialysate bagl.

11. Disconnect the water source at the luer connection 26

12. Connect the bag of dialysate solution to the dialysis circuit at theconnection 8. This leaves the filter 11 and permanent clamp 13 in placeto protect the water supply source.

13. Unclamp the line going to the dialysate bag (red clamp), andinitiate treatment after verifying that dialysate will be used within 24hours from when water was added.

Although the foregoing invention has, for the purposes of clarity andunderstanding, been described in some detail by way of illustration andexample, it will be obvious that certain changes and modifications maybe practiced that will still fall within the scope of the appendedclaims. For example, the devices and methods of each embodiment can becombined with or used in any of the other embodiments.

1. A tubing set for a renal replacement therapy system requiring asterile medicament, the tubing set comprising: a sterile filterconnectable to a fluid source to filter fluid passing therethrough andthereby yield an infusible grade sterile fluid, said filter being of aconfiguration to prevent pathogens from flowing across a membranethereof; a batch container having an interior volume and a first port;and a fluid line connected to the first port of the batch container,which is arranged such that the batch container interior volume canreceive the infusible grade sterile fluid from the sterile filter by wayof said fluid line, wherein the tubing set is adapted for one-time useat a location and a time at which a patient is to be infused with saidsterile medicament, and the fluid line includes at least one connectiontherein, a downstream connector of said connection being detachabletherefrom and in fluid communication with the batch container first portsuch that said infusible grade sterile fluid can be conveyed from thebatch container interior volume through said first port to a fluidcircuit of the renal replacement therapy system for use at a rate thatis independent of a rate permitted by said sterile filter when thedetachable connector is connected to the renal replacement therapysystem.
 2. The tubing set as in claim 1, further comprising a portionadapted to cooperate with a pump to convey fluid from said fluid sourcethrough said sterile filter.
 3. The tubing set as in claim 1, wherein aflow capacity of said sterile filter is less than a rate of consumptionof said sterile medicament required during infusion of said patient. 4.The tubing set as in claim 1, wherein said sterile filter is effectiveto block air bubbles in fluid from said fluid source from flowing intosaid batch container.
 5. The tubing set as in claim 1, wherein saidbatch container is fitted with at least one additional connector topermit it to be connected with at least one of a replacement fluidcircuit, a waste circuit, and a blood circuit of a blood treatmentcircuit, such that said sterile medicament can be recirculated throughsaid batch container to rid said at least one of the replacement fluidcircuit, the waste circuit, and the blood circuit of the blood treatmentcircuit of gas by settling said gas out of said sterile medicament intosaid batch container.
 6. The tubing set as in claim 1, wherein saidrenal replacement therapy includes at least one of hemofiltration andhemodiafiltration.
 7. The tubing set as in claim 6, further comprising aportion adapted to cooperate with a pump to convey fluid from said fluidsource through said sterile filter.
 8. The tubing set as in claim 6,wherein a flow capacity of said sterile filter is less than a rate ofconsumption of said sterile medicament required during infusion of saidpatient.
 9. The tubing set as in claim 8, wherein said sterile filter iseffective to block air bubbles in fluid from said fluid source fromflowing into said batch container.
 10. The tubing set as in claim 6,wherein said batch container is fitted with at least one additionalconnector to permit it to be connected with at least one of areplacement fluid circuit, a waste circuit, and a blood circuit of ablood treatment circuit, such that said sterile medicament can berecirculated through said batch container to rid said at least one ofthe replacement fluid circuit, the waste circuit, and the blood circuitof the blood treatment circuit of gas by settling said gas out of saidsterile medicament into said batch container.
 11. The tubing set as inclaim 1, wherein the fluid line includes a Y-connector having first andsecond inlet portions and an outlet portion, the first inlet portionbeing connected to said downstream connector, the outlet portion beingconnected to said first port, and the second inlet portion beingconnected to a second fluid line having a check valve therein.
 12. Atubing set for a renal replacement therapy requiring an sterilemedicament, the tubing set comprising: a sterile filter connectable to afluid source to filter fluid passing therethrough and thereby yield aninfusible grade sterile fluid, said filter being of a configuration toprevent pathogens from flowing across a membrane thereof and to blockair bubbles; and a batch container having an interior volume and a firstport; and a fluid line connected to the first port of the batchcontainer, which is arranged such that the batch container interiorvolume can receive the infusible grade sterile fluid from the sterilefilter by way of said fluid line, wherein the tubing set is adapted forone-time use at a location and a time at which a patient is to beinfused with said sterile medicament, the fluid line includes at leastone connection therein, a downstream connector of said connection beingdetachable therefrom and in fluid communication with the batch containerfirst port such that said infusible grade sterile fluid can be conveyedfrom the batch container interior volume through said first port to afluid circuit of the renal replacement therapy system when thedetachable connector is connected to the renal replacement therapysystem, and said batch container is fitted with at least one additionalconnection to permit recirculation of fluid through said fluid circuitto remove gas from said fluid circuit by permitting air to settle insaid batch container.
 13. The tubing set as in claim 12, furthercomprising a portion adapted to cooperate with a pump to convey fluidfrom said fluid source through said sterile filter.
 14. The tubing setas in claim 12, wherein a flow capacity of said sterile filter is lessthan a rate of consumption of said sterile medicament required duringinfusion of said patient.
 15. The tubing set as in claim 12, whereinsaid sterile filter is effective to block air bubbles in fluid from saidfluid source from flowing into said batch container.
 16. The tubing setas in claim 12, wherein the fluid line includes a Y-connector havingfirst and second inlet portions and an outlet portion, the first inletportion being connected to said downstream connector, the outlet portionbeing connected to said first port, and the second inlet portion beingconnected to a second fluid line having a check valve therein.